淫羊藿苷对快速老化小鼠SAMP8脑线粒体的保护作用

中国临床药理学与治疗学 ›› 2010, Vol. 15 ›› Issue (7): 721-726.

• 基础研究 • 下一篇

淫羊藿苷对快速老化小鼠SAMP8脑线粒体的保护作用

吴满刚¹, 贺晓丽², 强桂芬³, 时丽丽³, 李晓秀³, 祖勉³, 刘东华¹, 毕明刚², 杜冠华³

¹哈尔滨商业大学生命科学与环境科学研究中心,哈尔滨 150076,黑龙江;
²中国医学科学院药用植物研究所药理毒理研究中心,北京 100193;
³中国医学科学院药物研究所国家药物筛选中心,北京 100050

收稿日期:2010-05-24 修回日期:2010-06-29 出版日期:2010-07-26 发布日期:2020-09-15
通讯作者: 毕明刚,男,博士,副研究员,主要从事中药药理和免疫药理的研究。Tel: 010-62899739 E-mail: biminggang@yahoo.com.cn
作者简介:吴满刚,男,硕士研究生,主要从事神经药理的研究。 E-mail: wmg610@yahoo.cn
基金资助:
“重大新药创制”科技重大专项(2009ZX09301-003-11-2);国家自然科学基金项目(30772750)

Protective effects of icariin on cerebral mitochondria function in SAMP8 mice

WU Man-gang¹, HE Xiao-li², LIU Dong-hua¹, QIANG Gui-fen³, SHI Li-li³, LI Xiao-xiu³, ZU Mian³, BI Ming-gang², DU Guan-hua³

¹Life Science and Environment Science Research Center, Harbin University of Commerce, Herbin 150076, Heilongjiang,China;
²Research Center for Pharmacology and Toxicology, Chinese Academy of Medical Sciences & Peking Union Medical College Institute of Medicinal Plant Development, Beijing 100193,China;
³National Center for Pharmaceutical Screening, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050,China

Received:2010-05-24 Revised:2010-06-29 Online:2010-07-26 Published:2020-09-15

摘要/Abstract

摘要： 目的: 探讨淫羊藿苷(ICA)对快速老化小鼠SAMP8脑线粒体功能的影响。方法: 将8月龄快速老化小鼠SAMP8随机分为模型组、盐酸多奈哌齐 1 mg/kg 组、吡啦西坦 200 mg/kg组、ICA 75 mg/kg 组和 150 mg/kg组,每组6只;8只同月龄抗快速老化小鼠SAMR1作为正常对照组。给药 30 d 后,提取小鼠脑线粒体,测定线粒体呼吸功能、肿胀度、膜电位、活性氧(ROS)和ATP含量。结果: 与SAMR1正常对照组相比,SAMP8小鼠脑线粒体呼吸功能显著降低,表现为线粒体Ⅲ态呼吸明显降低,Ⅳ态呼吸改变不明显,呼吸控制指数和磷氧比值降低(P<0.05);线粒体膜肿胀度增高,膜电位降低,线粒体内ROS含量增高,而ATP含量明显降低(P<0.05)。与SAMP8模型组相比,ICA 75 mg/kg 和 150 mg/kg 均可明显改善SAMP8小鼠脑线粒体结构和呼吸功能(P<0.05,P<0.01)。结论: ICA可明显改善SAMP8小鼠脑线粒体结构和功能。

关键词: 淫羊藿苷, 快速老化小鼠, 阿尔茨海默病, 线粒体

Abstract: AIM: To investigate the protective effects of icariin (ICA) on cerebral mitochondria in senescence accelerated mice (SAM).METHODS: The 8-month-old senescence-accelerated mouse prone /8(SAMP8) mice were divided into SAMP8 group, Donepezil Hydrochloride (DON)-treated SAMP8 group (1 mg/kg), Piracetam (PIR)-treated SAMP8 group (200 mg/kg) and ICA-treated SAMP8 groups (75 mg/kg and 150 mg/kg). The age-matched senescence-accelerated mouse resistance 1( SAMR1) mice served as control. After treatment for 30 d, the cerebral mitochondria were isolated. The ATP production, reactive oxygen species (ROS) level, oxidative phosphorylation parameters and mitochondrial permeability transition pore (MPTP) were detected to evaluate the function of mitochondria in SAM mice.RESULTS: Respiratory control index, ADP/O ratio, State Ⅲ respiration and oxidative phosphorylation rate (OPR) were significantly lower in SAMP8 than those in SAMR1(P<0.05). State Ⅳ respiration did not significantly change in SAMP8 compared with that in SAMR1. At the same time, the loss of mitochondrial membrane potential(MMP), the decreased of ATP content, the increase of mitochondrial swelling degree and the increased level of ROS were also observed in SAMP8 brain mitochondria. ICA at the dosage of 75 mg/kg and 150 mg/kg significantly improved oxidative phosphorylation process, mitochondria swelling degree, MMP and other biochemical functions.CONCLUSION: ICA has a protective effect on cerebral mitochondrial impairment in SAMP8 mice.

Key words: Icariin, Senescence accelerated mice, Alzheimer's disease, Mitochondria

中图分类号:

R965.2

吴满刚, 贺晓丽, 强桂芬, 时丽丽, 李晓秀, 祖勉, 刘东华, 毕明刚, 杜冠华. 淫羊藿苷对快速老化小鼠SAMP8脑线粒体的保护作用[J]. 中国临床药理学与治疗学, 2010, 15(7): 721-726.

WU Man-gang, HE Xiao-li, LIU Dong-hua, QIANG Gui-fen, SHI Li-li, LI Xiao-xiu, ZU Mian, BI Ming-gang, DU Guan-hua. Protective effects of icariin on cerebral mitochondria function in SAMP8 mice[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2010, 15(7): 721-726.

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淫羊藿苷对快速老化小鼠SAMP8脑线粒体的保护作用

Protective effects of icariin on cerebral mitochondria function in SAMP8 mice

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